Short description

Depression treatment

Glutamatergic System

All conventional antidepressant drugs affect the neurotransmitters serotonin and norepinephrine. However, recent studies show that drugs affecting the messenger glutamate demonstrate a stronger and faster effect compared to conventional drugs. In a series of studies, we have demonstrated that the glutamate system is changed in patients with depression. These changes are believed to be the reason for the strong effect of glutamate drugs. In particular, Ketamine shows a strong antidepressant effect. Therefore, we started to use Ketamine at our ambulatory clinic (Bolligenstrasse) for the treatment of severe depression using specific treatment guidelines. The aim of our research is to evaluate the efficacy and safety of this treatment. Since Ketamine cannot be applied over a long term (due to side-effects), we are examining the well-tolerated substance N-acetylcysteine, which also influences the glutamatergic system. We are researching the efficacy, safety, and molecular biological mechanisms of drug action. We will investigate these mechanisms using positron emission tomography (in collaboration with ETH Zurich).

Paralysis of the frown lines

In recent years, three randomized, placebo-controlled studies have found a surprisingly large antidepressant effect in the paralysis of frown lines of the forehead by Botulinum toxin A (Botox) in depression. The average response rate was 54 percent. We plan to offer this treatment at our ambulatory clinic (Bolligenstrasse). In a scientific study, we want to determine why this therapy is so effective. The paralysis may lead to a suppression of negative emotions. We plan to investigate this through psychological experiments and EEG measurements. Further, the inhibited expression may improve social interactions. We plan to investigate this with regular, short smartphone-surveys. We will also consider whether the aesthetic effect strengthens the self-esteem of the depressive patient. The findings of this study will contribute to an optimal use of botulinum toxin A in depression.

Impartial understanding of social behavior

Recent studies regarding the career outcomes of depressed people show that disruptive social behavior is more decisive than classic depressive symptoms such as the depressive mood and sadness that usually occur only temporarily. Until now, there have been no simple, effective methods to reliably measure social behavior. Hence, the knowledge of the treatment of social behavior disorders is very low. In a series of studies using simple experiments, we have examined the social behaviors of depressive patients and patients with personality disorders. We have shown that, even after the amelioration of depression, patients avoid competitive situations. In follow-up studies, we aim to improve our social-measurement methods and develop therapeutic strategies to treat this avoidance.

Testing of anti-stigma campaigns

The majority of the population have a rather negative opinion about depression, leading to shame in people who suffer depression. This leads to inadequate treatment and difficulties during job-related reintegration. The stigma against depression is often implicit (an unconscious, automatic behavior). Previous anti-stigma campaigns did not show any improvement. To the contrary, they may have led to worsening outcomes. To clarify the effects of anti-stigma campaigns, we develop methods to measure implicit effects. This methodology will allow us to psychologically test campaigns before their general application.

Biomarkers

Leading experts agree that the discovery of biomarkers for mental disorders is of paramount importance to promote psychiatric research. Biomarkers are objective diagnostic indicators that improve diagnoses and facilitate the choice of therapies. Today different medications, psychotherapies, and treatment settings must be tested until the optimal therapy is found. Biomarkers help shorten this therapy-setting-process. Furthermore, biomarkers may help to develop new therapies that are specifically tailored to disease processes.

The greatest scientific success of our group in recent years has been the discovery of a glutamate receptor, mGluR5, as a biomarker for nicotine dependence. Using emission tomography, we showed that the amount of this receptor is 30 percent lower in a smoker’s brain. After more than five years of abstinence, the level of the receptor normalizes. A slow recovery of the receptor predicts a high recidivism rate. These findings inspired Novartis to investigate drugs targeting mGluR5 for addiction therapy.

In a series of studies, we have developed biomarkers that predict responses to conventional antidepressants. Our method allows researchers to determine whether a serotonin deficiency, a norepinephrine deficiency, or both are present. We were able to show the significance of these biomarkers in depression and in bulimia.

In an ongoing study, we are measuring a possible lack of dopamine as a biomarker for schizophrenia. The development of this biomarker will allow to selectively adjust antipsychotic drugs throughout the disease process.

In a large project (in collaboration with the University of Zurich and the Epigenetics Laboratory at the Mount Sinai School of Medicine in New York), we evaluate epigenetic alterations as biomarkers for mental disorders in the general population. Epigenetics refers to the modification of genes by environmental factors. Such markers allow us to better understand the role of social and genetic factors in the development of mental disorders. The results may help uncover efficient preventive and therapeutic measures.